In Silico Analysis of Nicotine's Molecular Targets in Parkinson's Disease.

IF 1.3 4区医学 Q4 PHARMACOLOGY & PHARMACY

Xenobiotica Pub Date : 2025-06-18 DOI:10.1080/00498254.2025.2519826

Hai Duc Nguyen

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引用次数: 0

Abstract

Purpose: we aimed to elucidate the molecular processes involved in how nicotine affects PD.

Methods: toxicogenomic, molecular mechanisms, physicochemical properties, pharmacokinetic profile, and biological activity were analyzed.

Results: We found that the therapeutic potential of nicotine in PD may be attributed to its ability to modulate the expression of 38 genes, especially GAPDH, TNF, IL6, and BDNF. The molecular mechanisms underlying the protective effects of nicotine against PD involve several pathways, including the "Parkinson's disease pathway", "the selenium micronutrient network", "the oxidative stress response", "dopamine binding", "Parkinsonian disorders", and "Lewy body disease". miRNAs like hsa-miRNA-203a-3p and miRNA-26b-5p and transcription factors like HNF4, MAPK3, and EVI1 explained how nicotine protects neurons from PD. An assessment was also carried out on drug candidates (polaprezinc) and miRNA sponges (hsa-miR-181a-5p, hsa-miR-124-3p, hsa-miR-1-3p) that may possess the capability to synergize the effects of nicotine. Nicotine's physicochemical properties, pharmacokinetic profile, and biological activity are conducive to its favorable attributes in the context of PD, including high gastrointestinal absorption, ability to penetrate the blood-brain barrier, non-P-glycoprotein nature, and antiparkinsonian effects.

Conclusion: Nicotine plays crucial roles in the pathophysiology of PD. Further work is needed to evaluate the impact of nicotine on non-motor symptoms.

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帕金森病中尼古丁分子靶点的计算机分析。

目的：我们旨在阐明尼古丁如何影响PD的分子过程。方法：从毒理学、分子机制、理化性质、药代动力学、生物活性等方面进行分析。结果：我们发现尼古丁对PD的治疗潜力可能归因于其调节38个基因表达的能力，特别是GAPDH、TNF、IL6和BDNF。尼古丁对PD保护作用的分子机制涉及多种途径，包括“帕金森病途径”、“微量元素硒网络”、“氧化应激反应”、“多巴胺结合”、“帕金森病”和“路易体病”。hsa-miRNA-203a-3p和miRNA-26b-5p等mirna以及HNF4、MAPK3和EVI1等转录因子解释了尼古丁如何保护神经元免受PD的影响。我们还对可能具有协同尼古丁作用的候选药物（polaprezinc）和miRNA海绵（hsa-miR-181a-5p、hsa-miR-124-3p、hsa-miR-1-3p）进行了评估。尼古丁的理化性质、药代动力学特征和生物活性有利于其在PD背景下的有利属性，包括高胃肠道吸收、穿透血脑屏障的能力、非p糖蛋白性质和抗帕金森作用。结论：尼古丁在PD的病理生理中起重要作用。需要进一步的工作来评估尼古丁对非运动症状的影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Xenobiotica 医学-毒理学

CiteScore

3.80

自引率

5.60%

发文量

审稿时长

2 months

期刊介绍： Xenobiotica covers seven main areas, including:General Xenobiochemistry, including in vitro studies concerned with the metabolism, disposition and excretion of drugs, and other xenobiotics, as well as the structure, function and regulation of associated enzymesClinical Pharmacokinetics and Metabolism, covering the pharmacokinetics and absorption, distribution, metabolism and excretion of drugs and other xenobiotics in manAnimal Pharmacokinetics and Metabolism, covering the pharmacokinetics, and absorption, distribution, metabolism and excretion of drugs and other xenobiotics in animalsPharmacogenetics, defined as the identification and functional characterisation of polymorphic genes that encode xenobiotic metabolising enzymes and transporters that may result in altered enzymatic, cellular and clinical responses to xenobioticsMolecular Toxicology, concerning the mechanisms of toxicity and the study of toxicology of xenobiotics at the molecular levelXenobiotic Transporters, concerned with all aspects of the carrier proteins involved in the movement of xenobiotics into and out of cells, and their impact on pharmacokinetic behaviour in animals and manTopics in Xenobiochemistry, in the form of reviews and commentaries are primarily intended to be a critical analysis of the issue, wherein the author offers opinions on the relevance of data or of a particular experimental approach or methodology